Human epithelial growth factor receptor 2 (HER2) status in primary and metastatic esophagogastric junction adenocarcinomas |
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Authors: | Fassan Matteo Ludwig Kathrin Pizzi Marco Castoro Carlo Guzzardo Vincenza Balistreri Mariangela Zaninotto Giovanni Ruol Alberto Giacomelli Luciano Ancona Ermanno Rugge Massimo |
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Affiliation: | a Department of Medical Diagnostic Sciences and Special Therapies (Pathology and Cytopathology Unit), University of Padova, 35100 Padova, Italyb Department of Oncology and Surgical Sciences, University of Padova, 35100 Padova, Italyc Istituto Oncologico Veneto-IOV-IRCCS, 35100 Padova, Italyd Department of Gastroenterological and Surgical Sciences, University of Padova, 35100 Padova, Italy |
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Abstract: | Differences in human epithelial growth factor receptor 2 dysregulation in primary solid tumors and metastases may (at least partially) explain human epithelial growth factor receptor 2-targeted therapeutic inconsistencies. Human epithelial growth factor receptor 2 status was tested in a series of 47 radically treated consecutive esophagogastric junction adenocarcinomas (male/female, 38/9; mean age, 67.9 years) in both primary cancers and paired synchronous nodal metastases. None of the patients received neoadjuvant therapy. For each case, 2 nonadjacent tissue samples from primary esophagogastric junction adenocarcinoma and 2 different metastatic nodes were considered (188 tissue samples in all). Human epithelial growth factor receptor 2 status was assessed by immunohistochemistry (PATHWAY-HER2/neu [4B5]; Ventana Medical Systems, Milan, Italy) and dual chromogenic in situ hybridization (duoCISH; DAKO, Glostrup, Denmark). Immunohistochemistry staining scores were nil in 22 tumors (47%), 1 (21%) in 10, 2 (13%) in 6, and 3 (19%) in 9. Human epithelial growth factor receptor 2 gene amplification (25.5%) was associated with more differentiated phenotype (Fisher exact test, P = .039) and advanced tumor stage (Fisher exact test, P = .015). Significant agreement was observed between human epithelial growth factor receptor 2 protein expression (immunohistochemistry) and human epithelial growth factor receptor 2 gene's amplification (chromogenic in situ hybridization) (κ = 0.84, P < .001). Both immunohistochemistry and chromogenic in situ hybridization documented an excellent intratumor agreement in human epithelial growth factor receptor 2 status (κ = 0.75, P < .001; κ = 0.88, P < .001, respectively). Human epithelial growth factor receptor 2 status was comparable in primary versus metastatic nodal cancers by both immunohistochemistry and chromogenic in situ hybridization (Cohen Φ, both P < .001). In esophagogastric junction adenocarcinomas, human epithelial growth factor receptor 2 status (as assessed by immunohistochemistry and/or chromogenic in situ hybridization) is virtually unaffected by intratumor variability; it is consistent with findings in nodal metastases, and it reliably identifies patients with esophagogastric junction adenocarcinoma eligible for anti-human epithelial growth factor receptor 2 therapy. |
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Keywords: | HER2 Immunohistochemistry ISH Adenocarcinoma |
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